Comparison of cyclic and linear analogs of vasoactive intestinal peptide.

A series of i-->i + 4 side-chain to side-chain lactam analogs of vasoactive intestinal peptide has been prepared in order to study the effect of cyclization on biological activity. In vitro, on guinea pig tracheal smooth muscle and on human bronchial tissue, approximately half of the cyclic analogs showed increased potency and half were decreased over the linear analogs. Several cyclic compounds were between 10- and 20-fold more potent and one was 290-fold more potent than the linear species.

Structure-activity studies on the vasoactive intestinal peptide pharmacophore. 1. Analogs of tyrosine.

From previous work, the primary functional groups, i.e. side chains, of the vasoactive intestinal peptide which are responsible for interaction with the VIP receptor have been identified.

Essential fatty acids are antagonists of the leukotriene B4 receptor.

A series of essential fatty acids and fatty acid derivatives were evaluated for their ability to inhibit [3H] leukotriene B4 (LTB4) binding to pig neutrophil membranes. The fatty acids varied in chain length, extent of unsaturation, position of unsaturation, and isomerization. Generally, fatty acids with two or more unsaturated sites and chain lengths of 18-22 were potent inhibitors of [3H]LTB4 binding; both n-3 and n-6 fatty acids were inhibitory.

Ro 25-1553: a novel, long-acting vasoactive intestinal peptide agonist. Part I: In vitro and in vivo bronchodilator studies.

Ro 25-1553, a cyclic peptide analog of vasoactive intestinal peptide (VIP), was designed to overcome many of the deficiencies inherent in this natural neuropeptide. On isolated guinea pig tracheal smooth muscle, Ro 25-1553 produces concentration-dependent relaxation of contractile responses to a number of different spasmogens. Depending on the contractile stimulus, Ro 25-1553 is 24 to 89 times more potent than VIP as a relaxant of guinea pig trachea.